John G. Koland, PhD

Portrait
Associate Professor of Pharmacology
Associate Professor of Internal Medicine

Contact Information

Primary Office
2-550 BSB
51 Newton Rd.
Iowa City, IA 52242
319-335-6508

Lab
2-551 BSB
Iowa City, IA 52242
319-335-6551

Education

BS, Chemistry, University of Minnesota
PhD, Chemistry, University of Illinois
Postdoctoral Fellow, Chemistry, Cornell University, Ithaca, NY

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Molecular Medicine

Research Summary

Research in the Koland laboratory focuses upon the signaling events elicited by members of the epidermal growth factor (EGF) receptor family (ErbB/HER family receptors). ErbB family receptors are among a larger group of receptors possessing intrinsic protein tyrosine kinase activity that is activated upon binding of polypeptide growth factors. ErbB receptors and their associated growth factor ligands play crucial roles in human cancer, and in the context of breast cancer, they are important diagnostic markers and the targets of new therapeutic agents. The Koland laboratory is investigating ErbB receptor signaling in mammary tumor cells by use of biochemical and biophysical approaches. One research initiative addresses the molecular mechanisms by which the intracellular protein tyrosine kinase domain of the EGF receptor is regulated by binding of growth factor to the receptor extracellular domain. Here the laboratory has developed novel fluorescent spectroscopic methods by which structural changes associated with receptor activation and phosphorylation can be detected. With these methods Dr. Koland's laboratory has demonstrated that phosphorylation of the receptor C-terminal domain alters its conformation and effects its displacement relative to the catalytic site. These findings are consistent with a model in which the C-terminal phosphorylation domain in the basal state interacts with the catalytic core of the kinase to inhibit its activity. In this model, phosphorylation of the C- terminal domain induces structural changes that relieve this inhibitory interaction and result in kinase activation. A more recent initiative explores how ErbB family members are spatially organized in the cell membrane at the sub-light microscopic level, and how this spatial microorganization might be perturbed in cancer cells. Here the laboratory seeks to determine whether ErbB receptors are confined to membrane microdomains of specific biochemical composition and how membrane microenvironment impacts upon receptor signaling. Approaches used include fluorescence microscopy and electron microscopy (EM). Preliminary EM studies indicate that ErbB receptors are in breast cancer cell membranes indeed localized in submicroscopic domains consistent with the size of lipid rafts.

Publications

Sarkar, M., Koland, J. G. (2016). Fluorescence recovery after photobleaching analysis of the diffusional mobility of plasma membrane proteins: HER3 mobility in breast cancer cell membranes. In M. Waugh (Eds.) Lipid Signaling Protocols. pp. 97-105. Lipid Signaling Protocols in series Methods Molecular Biology, Springer, New York.

Krager, K. J., Koland, J. G. (2016). Metabolically biotinylated reporters for electron microscopic imaging of cytoplasmic membrane microdomains. In M. Waugh (Eds.) In: Lipid Signaling Protocols. pp. 87-96. Methods Molecular Biology, Springer, New York.

Koland, J. G. (2014). Coarse-grained molecular simulation of epidermal growth factor receptor protein tyrosine kinase multi-site self-phosphorylation. PLoS Comput Biol, 10(1), e1003435. PMID: 24453959.

Krager, K. J., Sarkar, M., Twait, E. C., Lill, N. L. & Koland, J. G. (2012). A novel biotinylated lipid raft reporter for electron microscopic imaging of plasma membrane microdomains. Journal of lipid research, 53(10), 2214-25. PMID: 22822037.

Vaught, D. B., Stanford, J. C., Young, C., Hicks, D. J., Wheeler, F., Rinehart, C., Sanchez, V., Koland, J., Muller, W. J., Arteaga, C. L. & Cook, R. S. (2012). HER3 is required for HER2-induced preneoplastic changes to the breast epithelium and tumor formation. Cancer research, 72(10), 2672-82. PMID: 22461506.

Visser Smit, G. D., Place, T. L., Cole, S. L., Clausen, K. A., Vemuganti, S., Zhang, G., Koland, J. G. & Lill, N. L. (2009). Cbl controls EGFR fate by regulating early endosome fusion. Science signaling, 2(102), ra86. PMID: 20029031.

Lee, N. Y., Hazlett, T. L. & Koland, J. G. (2006). Structure and dynamics of the epidermal growth factor receptor C-terminal phosphorylation domain. Protein science : a publication of the Protein Society, 15(5), 1142-52. PMID: 16597832.

Lee, N. Y., Koland, J. G. (2005). Conformational changes accompany phosphorylation of the epidermal growth factor receptor C-terminal domain. Protein science : a publication of the Protein Society, 14(11), 2793-803. PMID: 16199664.

Monick, M. M., Cameron, K., Staber, J., Powers, L. S., Yarovinsky, T. O., Koland, J. G. & Hunninghake, G. W. (2005). Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis. The Journal of biological chemistry, 280(3), 2147-58. PMID: 15542601.

Koland, J. G., Twait, E. C. (2005). ErbB receptor signaling in cancer cell membrane microdomains. Department of Defense Breast Cancer Research Program.

Lee, N. Y., Hazlett, T. L. & Koland, J. G. (2005). Structure and dynamics of the epidermal growth factor receptor carboxy-terminal phosphorylation domain. Department of Defense Breast Cancer Research Program.

Koland, J. G. (2004). ErbB/HER receptor signaling: mechanisms of cellular transformation. University of Iowa Breast Cancer Symposium.

Vijapurkar, U., Kim, M. S. & Koland, J. G. (2003). Roles of mitogen-activated protein kinase and phosphoinositide 3'-kinase in ErbB2/ErbB3 coreceptor-mediated heregulin signaling. Experimental cell research, 284(2), 291-302. PMID: 12651161.

Lee, N. Y., Koland, J. G. (2003). Fluorescence studies of EGF receptor C-terminal domain conformation. ASBMB.

Odero-Marah, V. A., Khalkhali-Ellis, Z., Schneider, G. B., Seftor, E. A., Seftor, R. E., Koland, J. G. & Hendrix, M. J. (2002). Tyrosine phosphorylation of maspin in normal mammary epithelia and breast cancer cells. Biochemical and biophysical research communications, 295(4), 800-5. PMID: 12127964.

Park, H., Clark, E., Cullen, J. J., Koland, J. G., Kim, M. S. & Conklin, J. L. (2002). Expression of inducible nitric oxide synthase in the lower esophageal sphincter of the endotoxemic opossum. Journal of gastroenterology, 37(12), 1000-4. PMID: 12522530.

Hellyer, N. J., Kim, M. S. & Koland, J. G. (2001). Heregulin-dependent activation of phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 co-receptor. The Journal of biological chemistry, 276(45), 42153-61. PMID: 11546794.

Hansen, M. R., Vijapurkar, U., Koland, J. G. & Green, S. H. (2001). Reciprocal signaling between spiral ganglion neurons and Schwann cells involves neuregulin and neurotrophins. Hearing research, 161(1-2), 87-98. PMID: 11744285.

Tan, H., Kim, H. H. & Koland, J. G. (2000). Heregulin/ErbB receptor signaling in breast cancer cells. Department of Defense Breast Cancer Research Program.

Vijapurkar, U., Kim, H. H. & Koland, J. G. (1999). The ErbB3/HER3 receptor protein: signaling mechanisms and biologic function. Current Topics in Biochemical Research, 1, 37-57.

Vijapurkar, U., Kim, H. H. & Koland, J. G. (1999). The ErbB3/HER3 receptor protein: Signaling mechanisms and biologic function. Current Topics in Biochemical Research, 1, 37-57.

Hellyer, N. J., Cheng, K. & Koland, J. G. (1998). ErbB3 (HER3) interaction with the p85 regulatory subunit of phosphoinositide 3-kinase. The Biochemical journal, 757-63. PMID: 9677338.

Vijapurkar, U., Cheng, K. & Koland, J. G. (1998). Mutation of a Shc binding site tyrosine residue in ErbB3/HER3 blocks heregulin-dependent activation of mitogen-activated protein kinase. The Journal of biological chemistry, 273(33), 20996-1002. PMID: 9694850.

Kim, H. H., Vijapurkar, U., Hellyer, N. J., Bravo, D. & Koland, J. G. (1998). Signal transduction by epidermal growth factor and heregulin via the kinase-deficient ErbB3 protein. The Biochemical journal, 189-95. PMID: 9693119.

Cheng, K., Koland, J. G. (1998). Nucleotide-binding properties of kinase-deficient epidermal-growth-factor-receptor mutants. The Biochemical journal, 353-9. PMID: 9461530.

Vijapurkar, U. P., Kratz, D. A. & Koland, J. G. (1998). Role of PI 3-kinase and MAPK pathways in heregulin-stimulated mitogenesis by the ErbB2/ErbB3 coreceptor complex. Molecular Targets for Cancer.

Krieg, A. M., Matson, S., Cheng, K., Fisher, E., Koretzky, G. A. & Koland, J. G. (1997). Identification of an oligodeoxynucleotide sequence motif that specifically inhibits phosphorylation by protein tyrosine kinases. Antisense & nucleic acid drug development, 7(2), 115-23. PMID: 9149847.

Sierke, S. L., Cheng, K., Kim, H. H. & Koland, J. G. (1997). Biochemical characterization of the protein tyrosine kinase homology domain of the ErbB3 (HER3) receptor protein. The Biochemical journal, 757-63. PMID: 9148746.

Kratz, D., Koland, J. G. (1997). Growth inhibition of fibroblasts expressing the ErbB3/HER3 receptor protein by heregulin-neutralizing antibody. Growth Factor Signal Transduction Conference.

Kratz, D., Koland, J. G. (1997). Growth inhibition of fibroblasts expressing the ErbB3/HER3 receptor protein by heregulin-neutralizing antibody. University of Iowa College of Medicine Research Week.

Vijapurkar, U. P., Koland, J. G. (1997). Mutation of a Shc binding site tyrosine residue in ErbB3/HER3 blocks activation of mitogen-activated protein kinase by the ErbB2/ErbB3 heregulin coreceptor. University of Iowa College of Medicine Research Week.

Vijapurkar, U. P., Koland, J. G. (1997). Mutation of a Shc binding site tyrosine residue in ErbB3/HER3 blocks heregulin-dependent activation of mitogen-activated protein kinase. ASBMB.

Vijapurkar, U. P., Koland, J. G. (1997). Mutation of a Shc binding site tyrosine residue in ErbB3/HER3 blocks heregulin-dependent activation of mitogen-activated protein kinase. Growth Factor Signal Transduction Conference.

Hellyer, N. J., Cheng, K. & Koland, J. G. (1997). Role of protein domain interaction in p85 association with ErbB3. Growth Factor Signal Transduction Conference.

Koland, J. G., Vijapurkar, U. P. (1997). Signal transduction by the ErbB3/HER3 heregulin receptor. Department of Defense Breast Cancer Research Program.

Hellyer, N. J., Koland, J. G. (1996). Characterizing the interaction between ErbB3/HER3 and the p85 subunit of phosphatidylinositol 3-kinase with yeast two-hybrid system. ASBMB.

Shearer, M. C., Kim, H. H., Kratz, D. A. & Koland, J. G. (1996). Heregulin-dependent activation of MAP kinases in cultured rat astrocytes. ASBMB.

Cheng, K., Koland, J. G. (1996). Nucleotide binding by the epidermal growth factor receptor protein-tyrosine kinase. Trinitrophenyl-ATP as a spectroscopic probe. The Journal of biological chemistry, 271(1), 311-8. PMID: 8550578.

Hellyer, N. J., Kim, H. H., Greaves, C. H., Sierke, S. L. & Koland, J. G. (1995). Cloning of the rat ErbB3 cDNA and characterization of the recombinant protein. Gene, 165(2), 279-84. PMID: 8522190.

Gamett, D. C., Greene, T., Wagreich, A. R., Kim, H. H., Koland, J. G. & Cerione, R. A. (1995). Heregulin-stimulated signaling in rat pheochromocytoma cells. Evidence for ErbB3 interactions with Neu/ErbB2 and p85. The Journal of biological chemistry, 270(32), 19022-7. PMID: 7642563.

Cheng, K., Koland, J. G. (1995). 2'(3')-Trinitrophenyl-ATP as a novel substrate and spectroscopic probe for protein tyrosine kinases. ASBMB.

Kim, H. H., Hellyer, N. J., Sierke, S. L. & Koland, J. G. (1995). Epidermal growth factor-stimulated phosphorylation of the kinase-deficient ErbB3/HER3 protein. ASBMB.

Hellyer, N. J., Kim, H. H., Greaves, C. H., Sierke, S. L. & Koland, J. G. (1995). Molecular cloning of the rat erbB3 cDNA and characterization of the gene product. ASBMB.

Kim, H. H., Sierke, S. L. & Koland, J. G. (1994). Epidermal growth factor-dependent association of phosphatidylinositol 3-kinase with the erbB3 gene product. The Journal of biological chemistry, 269(40), 24747-55. PMID: 7929151.

Koland, J. G., Kim, H. H. & Sierke, S. L. (1994). Phosphorylation of the erbB3/HER3 gene product by the epidermal growth factor receptor. ASBMB.

Kim, H. H., Sierke, S. L. & Koland, J. G. (1994). Signal transduction by the erbB3 gene product: a putative receptor protein tyrosine kinase. Experimental Biology.

Sierke, S. L., Koland, J. G. (1993). SH2 domain proteins as high-affinity receptor tyrosine kinase substrates. Biochemistry, 32(38), 10102-8. PMID: 7691170.

Sierke, S. L., Longo, G. M. & Koland, J. G. (1993). Structural basis of interactions between epidermal growth factor receptor and SH2 domain proteins. Biochemical and biophysical research communications, 191(1), 45-54. PMID: 7680558.

Sierke, S. L., Koland, J. G. (1992). A chimeric protein incorporating an SH2 domain and the erbB3 C-terminus is a high affinity substrate for receptor tyrosine kinases. ASBMB.

Revis-Gupta, S., Abdel-Ghany, M., Koland, J. & Racker, E. (1991). Heparin stimulates epidermal growth factor receptor-mediated phosphorylation of tyrosine and threonine residues. Proceedings of the National Academy of Sciences of the United States of America, 88(14), 5954-8. PMID: 1712476.

Shinjo, K., Koland, J. G., Hart, M. J., Narasimhan, V., Johnson, D. I., Evans, T. & Cerione, R. A. (1990). Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42. Proceedings of the National Academy of Sciences of the United States of America, 87(24), 9853-7. PMID: 2124704.

Carraway, K. L., Koland, J. G. & Cerione, R. A. (1990). Location of the epidermal growth factor binding site on the EGF receptor. A resonance energy transfer study. Biochemistry, 29(37), 8741-7. PMID: 2271554.

Guy, P. M., Koland, J. G. & Cerione, R. A. (1990). Rhodopsin-stimulated activation-deactivation cycle of transducin: kinetics of the intrinsic fluorescence response of the alpha subunit. Biochemistry, 29(30), 6954-64. PMID: 2223753.

Koland, J. G., Cerione, R. A. (1990). Activation of the EGF receptor tyrosine kinase by divalent metal ions: comparison of holoreceptor and isolated kinase domain properties. Biochimica et biophysica acta, 1052(3), 489-98. PMID: 2354210.

Koland, J. G., O'Brien, K. M. & Cerione, R. A. (1990). Expression of epidermal growth factor receptor sequences as E. coli fusion proteins: applications in the study of tyrosine kinase function. Biochemical and biophysical research communications, 166(1), 90-100. PMID: 2154210.

Carraway, K. L., Koland, J. G. & Cerione, R. A. (1989). Visualization of epidermal growth factor (EGF) receptor aggregation in plasma membranes by fluorescence resonance energy transfer. Correlation of receptor activation with aggregation. The Journal of biological chemistry, 264(15), 8699-707. PMID: 2498317.

Koland, J. G., Cerione, R. A. (1988). Growth factor control of epidermal growth factor receptor kinase activity via an intramolecular mechanism. The Journal of biological chemistry, 263(5), 2230-7. PMID: 3257489.

Lorence, R. M., Koland, J. G. & Gennis, R. B. (1986). Coulometric and spectroscopic analysis of the purified cytochrome d complex of Escherichia coli: evidence for the identification of "cytochrome a1" as cytochrome b595. Biochemistry, 25(9), 2314-21. PMID: 3013299.

Koland, J. G., Hammes, G. G. (1986). Steady state kinetic studies of purified yeast plasma membrane proton-translocating ATPase. The Journal of biological chemistry, 261(13), 5936-42. PMID: 2871021.

Koland, J. G., Miller, M. J. & Gennis, R. B. (1984). Potentiometric analysis of the purified cytochrome d terminal oxidase complex from Escherichia coli. Biochemistry, 23, 1051-1056.

Koland, J. G., Miller, M. J. & Gennis, R. B. (1984). Reconstitution of the membrane-bound, ubiquinone-dependent pyruvate oxidase respiratory chain of Escherichia coli with the cytochrome d terminal oxidase. Biochemistry, 23(3), 445-53. PMID: 6367818.

Koland, J. G., Gennis, R. B. (1982). Proximity of reactive cysteine residue and flavin in Escherichia coli pyruvate oxidase as estimated by fluorescence energy transfer. Biochemistry, 21(18), 4438-42. PMID: 6751388.

Koland, J. G., Gennis, R. B. (1982). Identification of an active site cysteine residue in Escherichia coli pyruvate oxidase. The Journal of biological chemistry, 257(11), 6023-7. PMID: 7042705.

Koland, J. G., O'Brien, T. A. & Gennis, R. B. (1982). Role of arginine in the binding of thiamin pyrophosphate to Escherichia coli pyruvate oxidase. Biochemistry, 21(11), 2656-600. PMID: 7046791.

Koland, J. G., Mather, M. W., Gennis, R. B., White, J. S. & Hager, L. P. (1982). Activation of pyruvate oxidase and interaction with membrane components. In A. N. Martonosi (Eds.) Membrane and Transport. pp. 83-92. Plenum Press.

Mather, M., Blake, R., Koland, J., Schrock, H., Russell, P., O'Brien, T., Hager, L. P., Gennis, R. B. & O'Leary, M. (1982). Escherichia coli pyruvate oxidase: interaction of a peripheral membrane protein with lipids. Biophysical journal, 37(1), 87-8. PMID: 19431517.